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用于鉴定和筛选针对南非夸祖鲁-纳塔尔省呼吸道感染分离株的抗真菌药物的表型阵列

Phenotypic Array for Identification and Screening of Antifungals against Isolates from Respiratory Infections in KwaZulu Natal, South Africa.

作者信息

Naicker Sarla, Mohanlall Viresh, Ngubane Sandile, Mellem John, Mchunu Nokuthula Peace

机构信息

Department of Biotechnology and Food Science, Durban University of Technology, Durban 4000, Kwa-Zulu Natal, South Africa.

National Research Foundation, Pretoria 0001, Brummeria, South Africa.

出版信息

J Fungi (Basel). 2023 May 26;9(6):616. doi: 10.3390/jof9060616.

DOI:10.3390/jof9060616
PMID:37367552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10303164/
Abstract

The rapid emergence of invasive fungal infections correlates with the increasing population of immunocompromised individuals, with many cases leading to death. The progressive increase in the incidence of isolates is even more severe due to the clinical challenges in treating invasive infections in immunocompromised patients with respiratory conditions. Rapid detection and diagnosis are needed to reduce mortality in individuals with invasive aspergillosis-related infections and thus efficient identification impacts clinical success. The phenotypic array method was compared to conventional morphology and molecular identification on thirty-six species isolated from patients with respiratory infections at the Inkosi Albert Luthuli Hospital in Kwa-Zulu Natal. In addition, an antimicrobial array was also carried out to screen for possible novel antimicrobial compounds for treatment. Although traditional morphological techniques are useful, genetic identification was the most reliable, assigning 26 to species, 8 , and 2 including cryptic species of , . The phenotypic array technique was only able to identify isolates up to the genus level due to a lack of adequate reference clinical species in the database. However, this technique proved crucial in assessing a wide range of possible antimicrobial options after these isolates exhibited some resistance to azoles. Antifungal profiles of the thirty-six isolates on the routine azole voriconazole showed a resistance of 6%, with 61% having moderate susceptibility. All isolates resistant to the salvage therapy drug, posaconazole pose a serious concern. Significantly, was the only species resistant (25%) to voriconazole and has recently been reported as the species isolated from patients with COVID-19-associated pulmonary aspergillosis (CAPA). Phenotypic microarray showed that 83% of the isolates were susceptible to the 24 new compounds and novel compounds were identified for potentially effective combination treatment of fungal infections. This study also reports the first TR34/98 mutation in clinical isolates which is located in the gene.

摘要

侵袭性真菌感染的迅速出现与免疫功能低下个体数量的增加相关,许多病例导致死亡。由于在治疗患有呼吸道疾病的免疫功能低下患者的侵袭性感染方面存在临床挑战,分离株发病率的逐步上升更为严重。需要快速检测和诊断以降低侵袭性曲霉病相关感染个体的死亡率,因此有效的鉴定影响临床治疗的成功。将表型阵列方法与传统形态学和分子鉴定方法进行了比较,以鉴定从夸祖鲁-纳塔尔省因科西·阿尔伯特·卢图利医院呼吸道感染患者中分离出的36个物种。此外,还进行了抗菌阵列筛选,以寻找可能用于治疗的新型抗菌化合物。尽管传统形态学技术有用,但基因鉴定是最可靠的,鉴定出26个物种、8个……和2个……,包括……、……的隐性物种。由于数据库中缺乏足够的参考临床物种,表型阵列技术仅能将分离株鉴定到属水平。然而,在这些分离株对唑类药物表现出一些抗性后,该技术在评估广泛的可能抗菌选择方面被证明至关重要。36株分离株对常规唑类伏立康唑的抗真菌谱显示,耐药率为6%,61%具有中度敏感性。所有对挽救治疗药物泊沙康唑耐药的分离株都令人严重担忧。值得注意的是,……是唯一对伏立康唑耐药(25%)的物种,最近有报道称该物种是从新冠肺炎相关肺曲霉病(CAPA)患者中分离出来的。表型微阵列显示,83%的分离株对24种新化合物敏感,并鉴定出新型化合物可用于真菌感染的潜在有效联合治疗。本研究还报告了临床分离株中首次出现的位于……基因中的TR34/98突变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f5d/10303164/2dc20b137b88/jof-09-00616-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f5d/10303164/f7ce23631b39/jof-09-00616-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f5d/10303164/7c151ff85a91/jof-09-00616-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f5d/10303164/95094553c782/jof-09-00616-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f5d/10303164/2dc20b137b88/jof-09-00616-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f5d/10303164/f7ce23631b39/jof-09-00616-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f5d/10303164/7c151ff85a91/jof-09-00616-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f5d/10303164/95094553c782/jof-09-00616-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f5d/10303164/2dc20b137b88/jof-09-00616-g004.jpg

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